U.S. Food and Drug Administration Center for Food Safety and Applied Nutrition
Dietary supplements from plant sources are sometimes referred to as "phytopharmaceuticals." They are produced from fresh, dried or otherwise preserved plants or parts of plants.
The active ingredients are usually not completely isolated but rather are obtained along with other naturally occurring components of the plant. (These other components are often believed to influence the efficacy of the active ingredient.)
Sometimes the active ingredients are concentrated, and undesirable substances such as chlorophyll, tannins, or resins, are removed (List and Schmidt, 1989). The following sections discuss the various stages of production of dietary supplements of plant origin.
Cultivation and Collection of Plant Materials:
Most of the plants used for dietary supplements or medicinal purposes are cultivated, that is, grown on farms. Some, however, may be collected from the wild (Wijesekera, 1991). The following section discusses both methods for obtaining botanicals or herbals.
Cultivation allows producers to have more control over quality and purity than does collecting plants from the wild. Cultivars (cultivated varieties) of a number of medicinal plant species have been developed to produce high yields of the desired constituents. Some plants that are grown commercially for medicinal purposes are propagated vegetatively. (This means that new plants are grown from cuttings of old plants. Plants grown in this way are genetically identical to the parent plant.) Some medicinal plants are grown from selectively bred hybrid seeds, while others are varieties of plants that are unchanged from their natural form (Wijesekera, 1991).
A number of medicinal plants are cultivated for use by the pharmaceutical industry. Some examples include yams, which are used in the production of steroids; foxglove, which is used for digitalis; belladona, which is used for atropine; and opium, which is used to make morphine. The following is a list of major, commercially cultivated medicinal plants, many of which are used in dietary supplements (Wijesekera, 1991):
Aconites Costus Ipecac Rauvolfia Aloe Datura Lemon grass Senna Anise Dill Liquorice Smilax Artemisia Dioscorea Male fern Squill Basil Duboisia Mints Strophanthus Belladonna Ephedra Opium poppy Sweet flag Buchu Ergot Papain Thyme Casara bark Foxglove Periwinkle Valerian Celery Gentians Podophyllum Vinca Chamomilla Ginseng Polygala Withania Cinchona Henbane Psyllium Colchicum Hydrastis Pyrethrum
A number of countries commercially cultivate and export substantial quantities of medicinal plants. These countries include China, India, Thailand, South Korea, Brazil, Mexico, Egypt, Indonesia, Nepal, the Philippines, and Kenya. Eastern European countries cultivate medicinal plants as well, but mostly for their own consumption (Wijesekera, 1991).
As for any agricultural crop, producers of medicinal plants must provide plants with adequate moisture and nutrients and must control pests and diseases. Pesticides must be used cautiously to reduce the risk of harmful residues on plants (List and Schmidt, 1989).
Production of medicinal plants is generally labor intensive. In many cases, only the portions of the plant that contain the active ingredients -not the whole plant- are used. Sometimes harvesting involves picking leaves and flowers by hand (Hornok, 1992). In the future, tissue culture may be used for producing plant material (List and Schmidt, 1989).
Collection from the Wild:
Tropical forests are the source of a number of plants used for medicinal purposes. There are several disadvantages to collecting wild plants, however. This practice, along with deforestation, has caused some wild plant species to become endangered (Wijesekera, 1991).
Also, when plants are collected from the wild, there is a risk that they have been incorrectly identified (List and Schmidt, 1989). One advantage to using wild plants, however, is that they are unlikely to contain any pesticide residues (Wijesekera, 1991).
After the plants are harvested or gathered, they must be cleaned. Cleaning may involve screening, washing, peeling, or stripping leaves from stems. Any unnecessary parts are removed prior to drying to avoid wasting time and energy. Cleaning is often done by hand (Hornok, 1992).
In some cases, botanicals are used for extraction while fresh, but generally, they are dried first. The purpose of drying is to reduce the water content so that the plant can be stored. Most plants contain 60 to 80 percent moisture when harvested and must be dried to within 10 to 14 percent moisture before storage. Plants must be dried or processed as soon as possible after harvest because they begin to deteriorate immediately. Processing up to this point is generally done by the producer of the plants (Hornok, 1992). Plants can be dried naturally or by a number of artificial methods. The type of plant or plant part being used will determine the appropriate drying technique (List and Schmidt, 1989).
A practice that has been used since ancient times is sun-drying in the field. Although this method requires no drying equipment and uses solar energy, it requires large amounts of space, and plants can be damaged by the weather. Sometimes plants are placed by hand on drying frames or stands, to be air-dried in barns or sheds. This method of drying is labor-intensive and can take several weeks. The exact length of time for adequate drying depends on temperature and humidity (Hornok, 1992).
With the use of artificial dryers, drying time can be reduced to hours or minutes, and labor can also be greatly reduced. Fans that blow unheated air (cold-air drying) can reduce drying time to several days. Warm-air drying, which is the most widely used method for medicinal plants, uses a counter-current flow of warm air. There are several different types of systems for warm-air drying. One type is the plate chamber dryer, which blows warm air across plates on which plants have been placed. This method is useful for fragile flowers and leaves but requires large amounts of labor. Workers must load and unload the plants from the plates manually. The capacity of these dryers is relatively low, as well. Conveyor dryers are a commonly used type of warm-air dryer. Fresh plants travel on a conveyor belt through a counter-current flow of warm air. These dryers can operate continuously, require relatively little labor, and have high throughput. However, they require a large capital investment and have high energy requirements. The drying time required for conveyor dryers ranges from 2.5 to 6 hours, and the temperature of the drying air ranges from 40 to 80°C. Hot air dryers, which use very high temperatures (200 to 1,000°C) for very short periods (2 to 5 minutes) are not commonly used for drying medicinal plants (Hornok, 1992).
Packaging of Dried Plants:
Once drying is complete, plants are packaged in preparation for shipping and further processing. Dried herbaceous plants are generally compressed into bales weighing from 60 to 100 kg (13 to 220 pounds), which are then sewn into fabric bags or wrapped in plastic. Materials that cannot be baled, such as roots and bark, are placed in sacks. Smaller bags may be used for dense materials such as dried fruits or seeds. Very fragile materials, such as flowers, are packaged in crates. Dried plant materials tend to be hygroscopic (readily absorbing moisture) and must be stored under controlled humidity. Highly hygroscopic materials are generally packed in plastic (Hornok, 1992).
Cleaning and Sorting:
When the sacks or bales arrive at the processing facility, processors open the packages and clean the dried plants to remove as many impurities as possible. Sand is removed pneumatically and iron-containing metals are removed magnetically. Next, processors sort the plant pieces by size, since different end-uses require different particle sizes. For example, finely shredded material may be used for tea bags and somewhat less finely shredded material for loose teas or infusions, while coarsely shredded material may be sold directly to consumers or used for extraction. Particles that are already the desired size can go directly into storage to await further processing. Particles that are too big undergo additional grinding, cutting or shredding, and sieving. Various methods are used to reduce particle size including hammer action, pressure, friction, impact cutting, and shredding (List and Schmidt, 1989). Some plant materials are packaged and sold at this point without any additional processing. Some proceed through an extraction process, which the following section describes.
Extraction is a process whereby the desired constituents of a plant are removed using a solvent. The following section describes several methods used for preparing extracts, including organic solvent extraction, supercritical gas extraction, and steam distillation.
Organic Solvent Extraction:
Organic solvent extraction is one process for separating the desired substance from plant material. As was previously mentioned, dried plants are usually used for extraction, although fresh plants are sometimes used. The plants are first ground and then thoroughly mixed with a solvent such as hexane, benzene, or toluene inside a tank. The choice of solvent depends on several factors including the characteristics of the constituents being extracted, cost, and environmental issues. If the end product will contain trace amounts of residual solvent, a nontoxic solvent must be used. Once the solvent dissolves the desired substances of the plant, it is called "miscella." The miscella is then separated from the plant material (Hornok, 1992). There are a number of techniques for solvent extraction, which include maceration, percolation, and countercurrent extraction. The following is a brief description of each.
This method involves soaking and agitating the solvent and plant materials together. The solvent is then drained off. Remaining miscella is removed from the plant material through pressing or centrifuging. This method does not totally extract the active ingredients from the plant materials.
With this method, the plant material is moistened with solvent and allowed to swell before being placed in one of a series of percolation chambers. The material is repeatedly rinsed with solvent until all the active ingredient has been removed. Solvent is reused until it is saturated. New solvent is used on plant material that is almost completely exhausted, and then re-used on subsequently less exhausted batches. This method is more effective at removing active ingredients than the maceration technique.
This is a highly effective process whereby solvent flows in the opposite direction to plant material. Unlike maceration and percolation, which are batch processes, this method is continuous. Screw extractors and carousel extractors are two types of equipment used for countercurrent extraction (Wijesekera, 1991).
Purification and Concentration of Miscella:
Miscella that has been separated from the plant material generally contains some unwanted substances such as tannins, pigments, microbial contaminants, or residual solvent. Methods such as decanting, filtration, sedimentation, centrifuging, heating, adsorption, precipitation, and ion exchange are used to separate impurities from the miscella. Sometimes the miscella resulting from solvent extraction is used as the final dosage form. This is known as a "fluid extract" (List and Schmidt, 1989). The miscella is sometimes concentrated in order to increase the proportion of the desired substance. This is done through evaporation or vaporization. Solvent is generally recovered and reused (List and Schmidt, 1989). The degree of concentration depends on the desired end product. Equipment for concentrating the miscella may include descending film, thin layer or plate concentrators. Any method used to concentrate the miscella must avoid excessive heat because the active compounds may be subject to degradation (Wijesekera, 1991).
Sometimes extracts are dried completely using vacuum freeze dryers, cabinet vacuum dryers, continuously operating drum or belt dryers, microwave ovens, or atomizers. The technique for drying depends on the stability of the product and the amount of moisture that must be removed. The resulting powdered extract is less subject to microbial contamination than are liquid extracts (Hornok, 1992).
Extraction with Supercritical Gases:
This is a method for extracting active ingredients using gases. The plant material is placed in a vessel that is filled with a gas under controlled temperature and high pressure. The gas dissolves the active ingredients within the plant material, then passes into a separating chamber where both pressure and temperature are lower. The extract precipitates out and is removed through a valve at the bottom of the chamber. The gas is then reused. Gases suitable for supercritical extraction include carbon dioxide, nitrogen, methane, ethane, ethylene, nitrous oxide, sulfur dioxide, propane, propylene, ammonia, and sulfur hexafluoride. An advantage of supercritical extraction is that it can take place at low temperature, thus preserving the quality of temperature-sensitive components (List and Schmidt, 1989).
Steam distillation is another method for extracting active ingredients from medicinal plants. The plant material is loaded onto perforated plates inside a cylindrical tank or still, and steam is injected from below. The steam dissolves the desired substances in the plant, then enters a condenser where it is condensed back into a liquid. This condensate then passes into a flask, where the extract either rises to the top or settles to the bottom and is separated from the water. Distillation is complete when there is no more extract present in the condensate. The water may be reused, and the extract is purified through centrifuging and filtering (Hornok, 1992). Other Minor Extraction Methods. Other minor methods for making extracts include cold pressing and the enfleurage process.
Cold pressing is a process used to extract essential oils from citrus plants through pressing (Hornok, 1992). The enfleurage process is the same as the technique used to make perfume from flowers: purified fats are used to extract essential oils from plant parts. Plant material is spread onto sheets of purified fat, which dissolve the essential oils (List and Schmidt, 1989). Sometimes practitioners of herbal medicine prepare extracts for immediate use. These include aqueous extracts known as decoctions, infusions, or macerations. Plant material is mixed, agitated, and soaked in water to dissolve the active ingredients. Controlling microbial contamination can be difficult in aqueous extracts.
Oily drug extracts, also called "medicinal oils," may be prepared by soaking or macerating the plant material in an oil such as almond, peanut, olive, poppy seed, apricot kernel, or peach kernel oil. Vinegar is sometimes used to extract active ingredients as well. Plant materials are soaked in acetic acid, and the vinegar is consumed as the final dosage form (List and Schmidt, 1989).
Controlling the Quality of Extracts:
Once an extract has been produced by one of the methods mentioned above, producers can use a number of tests to evaluate the quality and purity of their product. First, they may examine the physical characteristics of the extract. This may include evaluating its appearance, pH, solubility, total solids content, ash content, and in the case of dried extracts, particle size.
Next, they may analyze the components of the extract to be certain it contains the appropriate quantities of desired ingredients. Chromatography (including thin layer, column, high pressure liquid, and gas chromatography) may be used for this.
Finally, they may test the extract for impurities such as residual solvents, herbicides, and pesticides and for microbial contamination (Wijesekera, 1991).
Some extracts are labeled and sold as standardized extracts. According to industry sources, the desired constituents in standardized extracts are measured and are listed as a percentage of the total weight of the extract. For example, echinacosides are the desired compounds present in echinacea extract. A capsule containing 250 mg of echinacea extract standardized to 4 percent would contain 10 mg of echinacosides. In some cases, the desired constituent is a known active ingredient.
In cases where the active ingredient has not been identified, another "marker " compound, or substance that is known to be present in the plant, may be measured for the purpose of standardization. Spectrophotometric testing and high pressure liquid chromatography may be used to measure standardized constituents (Standardized Extract Product Guide, 1997).